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At least 55 records · Page 3Linked to original sources

Determination of the developmental toxicity potential of butoxypropanol in rabbits after topical administration.

The developmental toxicity (embryofetotoxicity or teratogenicity) and maternal toxicity of butoxypropanol, a propylene glycol ether, was evaluated in New Zealand White rabbits. Dosages of 0 (water), 10, 40 or 100 mg/kg/day, selected on the basis of the water solubility of butoxypropanol and the results of a pilot study, were administered percutaneously to groups of artificially inseminated (Day 0) female rabbits on Days 7 through 18 of gestation. The dosage volume was 2 ml/kg. The control group contained 17 does and each test group contained 19 does. Does were observed for signs of test substance effect on abortion or premature delivery, body weight, and feed consumption. On Day 29, they were euthanized and examined for pregnancy, number and placement of implantations, early and late resorptions, and live fetuses. Pregnancy occurred in 15 control does (88%) and in 16 does in each test group (84%). There were no statistically significant differences between test and control groups for maternal body weight gain, feed consumption, number of corpora lutea per ovary, implantations, live fetuses, early and late resorptions, fetal body weights, gender, or gross external changes. There were no visceral or skeletal fetal alterations at any dose tested. No signs of maternal toxicity were observed; however, mild erythema occurred at the site of application at the 100 mg/kg/day dose level. The developmental no-effect level was greater than 100 mg/kg/day.

Administration, Topical↗

Gas chromatographic-mass spectrometric determination of two new antimycotic agents, 1-[(5-chloro-2-benzofuranyl)(2-chlorophenyl)methyl]-1H-imidazole and 1-[(5-bromo-2-benzofuranyl)phenylmethyl]-1H-imidazole, in rabbit plasma following topical administration: a preliminary comparison with bifonazole.

A method for the analysis of the antimycotic drugs 1-[(5-chloro-2-benzofuranyl)(2-chlorophenyl)methyl]-1H-imidazole, 1-[(5-bromo-2-benzofuranyl)phenylmethyl]-1H-imidazole and bifonazole in rabbit plasma, employing gas chromatography-mass spectrometry with selected-ion monitoring, was developed. The procedure involved single-step purification of the biological matrix via liquid-liquid extraction on Extrelut columns and use of a carrier substance to minimize the negative effects of adsorption sites during the gas chromatographic process. The limits of detection ranged from 0.1 to 1.4 ng/ml, starting from a 200-microliter sample. The method was applied to a preliminary evaluation of percutaneous absorption of both drugs in the rabbit after a single administration, in comparison with bifonazole.

Administration, Topical↗

Mitomycin concentration in rabbit and human ocular tissues after topical administration.

The authors measured mitomycin C (MMC) concentrations in ocular tissues with high-performance liquid chromatography. Mitomycin C concentration after a single subconjunctival injection of the drug in rabbit eyes showed a rapid decrease with a half-life of 0.18 to 0.30 hours for the conjunctiva and 0.20 to 0.45 hours for the sclera at the injection site. Irrigating the ocular surface with 200 ml of saline after MMC application reduced the initial drug concentration to one fifth in the sclera and to one fifteenth in the conjunctiva but did not change the half-life. The MMC concentration in human trabeculectomy specimens obtained immediately after MMC application (0.2 mg/0.5 ml) and irrigation was 5.4 to 12.0 micrograms/g with a mean of 8.4 micrograms/g, a level similar to that in the rabbit sclera immediately after the irrigation after administration of the same MMC dose. These results indicate that MMC disappears rapidly from the ocular tissues and that irrigating the tissues significantly reduces the tissue concentration of MMC.

Administration, Topical↗

Otrivine-antistin-pupil, corneal and conjunctival responses to topical administration.

The ocular effects of Otrivine-Antistin eyedrops have been measured in a placebo controlled single-blind study in sixteen healthy volunteers. The drops produced mild sympathomimetic responses in the eye but had no effect on corneal sensitivity or on intraocular pressure. The evidence indicates that use of Otrivine-Antistin imposes no risk to the subject.

Administration, Topical↗

Topical administration of prostaglandin E1 with iontophoresis for skin flap viability.

This study was performed to investigate the capability of iontophoretic delivery of prostaglandin E1 (PGE1) and the effect of this treatment on the viability of skin flaps on the rat dorsum model as described by Hammond and Ronald in 1993. The PGE1 level in the tissue sample under the electrode was assessed with radioimmunoassay. The iontophoretic treatment (for 20 minutes at 4 mA) with PGE1 solution (20 micrograms PGE1 in 2 ml saline) showed a significant increase of PGE1 in the flap tissue under the negative electrode (p < 0.05). Very little increase was observed after the iontophoresis of saline alone. This was not statistically significant. Iontophoretic treatment was given for 5 consecutive days following flap elevation. The survival area on the seventh postoperative day was significantly greater in the PGE1-treated flaps than that of either the control or saline-treated flaps. These results confirm the beneficial effect of iontophoretic treatment with PGE1 on the augmentation of skin flap viability.

Administration, Topical↗

Influence of topical administration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds.

Injury triggers a series of physiological events at the wound site. These include an inflammatory response that is established shortly after the injury, which is then followed by an intense formation of tissue over a period of days. Poly- and monounsaturated fatty acids exert major functions on the inflammatory responses, either in the form of phospholipids anchored in the cell membrane or as soluble lipoic mediators. We present evidence that linolenic (n-3), linoleic (n-6), and oleic (n-9) fatty acids can modulate the closure of surgically induced skin wounds. We found that n-9 fatty acids induced faster wound closure when compared to n-3, n-6, and control. In addition, n-9 fatty acids strongly inhibited the production of nitric oxide at the wound site. A mild improvement on wound closure was observed in the n-6 fatty acid-treated animals concurrent with a peak in nitric oxide production at 48 hours postsurgery. N-3 fatty acid treatment significantly delayed wound closure. Furthermore, we showed that n-3 fatty acid induced a peak in nitric oxide at 3 hours postsurgery and an intense deposition of extracellular matrix after 5 days of treatment. Thus, our results suggest a relevant role and potential therapeutic implication for fatty acids on skin wound healing.

Administration, Topical↗

The labelling index is not always reliable. Discrepancies between the labelling index and the mitotic rate in the rat corneal epithelium after intraperitoneal and topical administration of tritiated thymidine and colcemid.

Many cell kinetic studies are based on the assumption that tritiated thymidine injected into an animal is available for incorporation into DNA for only a short time, and that it labels all cells in the S phase. The present study indicates that this is not the fact for the rat corneal epithelium. The labelling index (LI) declines considerably from the limbal area to the central cornea, while the mitotic rate is almost constant all over the corneal epithelium. The LI should therefore not be used as the only criterion in the assessment of proliferation rate.

Administration, Topical↗